Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex

Fleur Bossi, Fabio Fischetti, Valentina Pellis, Roberta Bulla, Elisabetta Ferrero, Tom Eirik Mollnes, Domenico Regoli, Francesco Tedesco

Research output: Contribution to journalArticle

Abstract

The infrequent occurrence of septic shock in patients with inherited deficiencies of the terminal complement components experiencing meningococcal disease led us to suspect that the terminal complement complex is involved in vascular leakage. To this end, the permeabilizing effect of the cytolytically inactive soluble terminal complement complex (SC5b-9) was tested in a Transwell system measuring the amount of fluorescein-labeled BSA (FITC-BSA) leaked through a monolayer of endothelial cells. The complex caused increased permeability to FITC-BSA after 15 min as opposed to the prompt response to bradykinin (BK). The effect of SC5b-9 was partially reduced by HOE-140 or CV-3988, two selective antagonists of BK B2 and platelet-activating factor receptors, respectively, and was completely neutralized by the mixture of the two antagonists. Also, DX-88, a specific inhibitor of kallikrein, partially inhibited the activity of SC5b-9. The permeabilizing factor(s) released after 30 min of incubation of endothelial cells with SC5b-9 caused a prompt leakage of albumin like BK. Intravital microscopy confirmed both the extravasation of circulating FITC-BSA across mesenteric microvessels 15 min after topical application of SC5b-9 and the complete neutralization by the mixture of HOE-140 and CV-3988. SC5b-9 induced opening of interendothelial junctions in mesenteric endothelium documented by transmission electron microscopy.

Original languageEnglish
Pages (from-to)6921-6927
Number of pages7
JournalJournal of Immunology
Volume173
Issue number11
Publication statusPublished - Dec 1 2004

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Complement Membrane Attack Complex
Kinins
Platelet Activating Factor
Blood Vessels
Bradykinin
Endothelial Cells
Kallikreins
Septic Shock
Microvessels
Fluorescein
Transmission Electron Microscopy
Endothelium
Albumins
Permeability
fluorescein isothiocyanate bovine serum albumin
icatibant
CV 3988

ASJC Scopus subject areas

  • Immunology

Cite this

Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. / Bossi, Fleur; Fischetti, Fabio; Pellis, Valentina; Bulla, Roberta; Ferrero, Elisabetta; Mollnes, Tom Eirik; Regoli, Domenico; Tedesco, Francesco.

In: Journal of Immunology, Vol. 173, No. 11, 01.12.2004, p. 6921-6927.

Research output: Contribution to journalArticle

Bossi, Fleur ; Fischetti, Fabio ; Pellis, Valentina ; Bulla, Roberta ; Ferrero, Elisabetta ; Mollnes, Tom Eirik ; Regoli, Domenico ; Tedesco, Francesco. / Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. In: Journal of Immunology. 2004 ; Vol. 173, No. 11. pp. 6921-6927.
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